The characteristic of microorganisms to form biofilms on surfaces, gives numerous problems. The biofilm is a collection of microcolonies with water channels in between and an assortment of cells and extra cellular polymers (glycoproteins, polysaccharides and proteins). Once the microorganisms (bacteria) adhere, they can multiply, form complex multilayered colonies, and produce a slimy matrix material that encases the bacterial cells.
In nutrient-limited ecosystems, such as the aquatic environments, bacteria have a marked tendency to attach to surfaces and initiate the formation of a biofilm. Biofilms routinely foul ship hulls, submerged oil platforms, and the interiors of pipe works and cooling towers. The damage caused by these wildly procreating bacteria includes corrosion and failure of metal components.
Biofilm formation is also a serious medical problem that manifests itself as biomaterial-associated infections of devices such as endotracheal tubes, intravenous catheters, urinary catheters, and contact lenses, and of prosthetic implants. In fact, the increased use of biomedical devices and implants in humans in recent years has resulted in a concomitant rise in bacterial infections. Depending on the organism involved, these infections can be acute (symptoms appear relatively soon after material insertion) or chronic (may take months for symptoms to appear). The formation of a biomaterial-associated biofilm (irreversible infection) usually leads to removal or revision of the affected device or implant, with obvious devastating results for the patient.
Further, biofilms are also a severe problem in oral health since they can cause dental diseases including dental plaque. Dental plaque is the result of adhesion and colonization by different bacteria on the dental surface. Dental plaque consists of a three-dimensional organized dynamic structure of one or more microorganism species, which are irreversibly attached to the dental enamel, whereon they form an extra-cellular matrix. This type of biofilm mainly appears in between and at the bottom of the teeth (against the gums) where the mechanical removal is hampered. The biofilm mainly consists of bacteria, extra-cellular polysaccharides (EPS=biofilm matrix) and water. This biofilm may lead to tooth demineralization, gingivitis, periodontitis and even systemic complications.
Immediately after brushing one's teeth a conditioning film arises on the tooth surface that mainly consists of saliva elements and food remainders. Primary oral bacterial colonizers, especially Streptococci, e.g. Streptococcus mutans, S. sanguinis, S. mitis. S. sobrinus and S. salivarius, attach to this conditioning film. These bacteria convert sucrose into sticky glucans onto the dental surface. These bacteria produce extra-cellular glucosyltransferases (GTF), enzymes that catalyze the splitting of sucrose into fructose and glucose. Fructose can further be converted into lactate, which results in an oral pH drop that can lead to reversible solution of calcium ions and demineralization of the dental surface. Glucose is transferred to a glucose polymer (dextran chain) and thus forms part of the extra-cellular polysaccharides (EPS), which form an ideal culture medium for a dental biofilm. Other bacteria find shelter in this biofilm and may become sedentary. The said bacteria ferment food remains, which results in a decreased oral pH and leads to a demineralization of the dental surface. When the pH recovers, calcium mineralizes back out of the saliva to the dental enamel and eventual calcify the dental plaque into a persistent dental tartar or calculus.
The development of effective agents for controlling micro-organism biofilms adherent to cell surfaces has proven problematic. A biofilm is in part difficult and often impossible to eradicate with antibiotics, in part because the slime matrix acts as a physical and chemical barrier to protect the bacteria. Antimicrobial agents such as antibiotics and other drugs inhibiting bio-adhesion are often not able to remove the biofilm.
In the case of dental plaque for instance, current treatment consists of mechanical removal and/or chemical killing of biofilm bacteria. In the latter treatment, all germs in the oral flora are killed, which leads to a disruption of the natural, microbial oral homeostasis. Moreover, such treatment has the disadvantage that, by killing biofilm bacteria, the released ecological niche can be occupied by detrimental yeast species and/or fungi, e.g. Candida sp.
Another problem in treating biofilm is the occurrence of resistance of biofilm bacteria against antimicrobial agents. It is troubling that the biofilm phenotype of some species has been shown to differ radically from the planktonic phenotype of the same organism. One of the facets in which biofilm bacteria differ the most profoundly from their planktonic counterparts, is in the critical matter of resistance to antibacterial agents. Biofilm cells are more resistant than planktonic cells. This is believed to be due to more than just a physical protection by the biofilm matrix. Bacteria in biofilm seem to posses an altered physiology and mode of growth. Bacteria in biofilm are all together a distinct phenotype with altered gene expression as compared to the same species in planktonic phase.
In view of the above, it can be seen that there remains a great need in the art for compositions and methods able to prevent or inhibit the formation of biofilms.
It is therefore a main object of the present invention to provide effective compounds, compositions, and methods for preventing and/or inhibiting biofilm formation.
It is yet another object of the invention to provide compounds, compositions for preventing and/or inhibiting biofilm formation, which are not bactericidal.
It is a preferred object of the invention to provide effective compounds, compositions, and methods for preventing and/or inhibiting biofilm formation on dental surfaces in the oral cavity. More particularly, it is an object of the present invention to provide an improved oral health product, which prevents or inhibits dental biofilm formation.
In another object, the present invention aims to provide compounds, compositions, and methods for the treatment and/or prevention of dental plaque, dental tartar and/or dental diseases related thereto.